The objective of this investigation is to clearly delineate, at the cellular and molecular level, the immunogenesis of the humoral anti-erythrocyte autoantibody response - the primary pathogenetic effector of autoimmune hemolytic anemia. These studies, utilizing NZB mice, will include: 1) purification and characterization of the pathogenetic erythrocyte autoantigen; 2) characterization of interactions between the lymphoid system and autoantigen; 3) delineation of the role of the X autoantigen molecule in the initiation, regulation and genetic segregation of the anti-erythrocyte autoantibody response; 4) characterization of the B lymphocyte events and delineation of focal aberrations and critical points of control of specific B lymphocyte kinetics; and 5) delineation of the influence of regulatory mechanisms, including T lymphocytes and other "host factors", which are responsible for the initiation and regulation of B lymphocyte proliferatton and derepression intrinsic to the synthesis of pathogenetic autoantibody and the pathogenesis of autoimmune hemolytic anemia. BIBLIOGRAPHIC REFERENCES: DeHeer, David H., and Edgington, Thomas S.: Estimation of relative antibody affinity at the level of the antibody-secreting cell during maturation of the immune response. Cellular Immunol. 18: 466-475, 1975. DeHeer, David H., and Edgington, Thomas S.: Aberrant maturational characteristics of the immune responses of NZB mice to autologous and heterologous antigens. Cellular Immunol. 19: 183-193, 1975.